Ionizing radiation causes mutation, transformation, and lethal effects in living systems. DMA damage is intimately involved in these effects. The long term goals of this work are to clarify the radiation chemical mechanisms by which DNA damage is produced by ionizing radiation in the cellular environment, and by which it may be modified and repaired. This will permit an evaluation of the ability of cellular systems to cope with this damage, and also provide the means to design improved methods of influencing these processes, for example with radiosensitizers and radioprotectors The nature and spatial distribution of the DNA damage products is strongly influenced by the ionization mechanism, the clustering of the ionization events, and also by the presence of nearby chemical species such as amino acid residues in DNA binding proteins. These effects of these processes are understood in isolation but not in combination. Our approach uses adaptable model systems with which we can adjust the processes individually. We use oligo-arginines, the lac represser, and histones to examine the effects of DNA binding proteins. The DNA damage is detected as in general as strand breaks or base damages in plasmid targets, and also as the particular low molecular weight products 5-methylenefuanone and 8-oxo-7,8-dihydroguanine which can be identified chromatographically. Because the DNA damage is produced under controlled conditions, we can make a quantitative description of the processes in terms of rate constants and lifetimes of intermediates. The result will be an improved understanding of how DNA damage is produced under physiological conditions. With a renewed emphasis on nuclear power, debate over long term storage of radioactive waste, and terrorism related issues, there is a substantial concern about the hazards associated with ionizing radiation. Rational risk estimation requires an understanding of the mechanisms involved. Applications to human health include defining the causes of individual variation in radiosensitivity and the development of mechanistic models for risk estimation of cancer etiology by low dose and low dose rate exposures.